biostudies-literatureHadland BNIDDK NIH HHSNHLBI NIH HHSEuropean Hematology AssociationU.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood InstituteAmerican Society of HematologyNCI NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases1584https://www.ebi.ac.uk/biostudies/studies/S-EPMC8948249biostudies-literatureUnknown13(1)Hematopoietic stem cells (HSCs) develop from hemogenic endothelium within embryonic arterial vessels such as the aorta of the aorta-gonad-mesonephros region (AGM). To identify the signals responsible for HSC formation, here we use single cell RNA-sequencing to simultaneously analyze the transcriptional profiles of AGM-derived cells transitioning from hemogenic endothelium to HSCs, and AGM-derived endothelial cells which provide signals sufficient to support HSC maturation and self-renewal. Pseudotemporal ordering reveals dynamics of gene expression during the hemogenic endothelium to HSC transition, identifying surface receptors specifically expressed on developing HSCs. Transcriptional profiling of niche endothelial cells identifies corresponding ligands, including those signaling to Notch receptors, VLA-4 integrin, and CXCR4, which, when integrated in an engineered platform, are sufficient to support the generation of engrafting HSCs. These studies provide a transcriptional map of the signaling interactions necessary for the development of HSCs and advance the goal of engineering HSCs for therapeutic applications.Nature communicationsEngineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics.PMC8948249NAR35 HL150809R01DK110563K08HL140143P30 CA015704TRTH153RC2DK114777R01 DK110563RC2 DK114777K08 HL140143Bernstein IDButler JMNourigat-McKay CIshida THadland BTrapnell CVarnum-Finney BDozono SJackson DLItkin THeck AMRafii SDignum TfalseEngineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics.Hematopoietic stem cells (HSCs) develop from hemogenic endothelium within embryonic arterial vessels such as the aorta of the aorta-gonad-mesonephros region (AGM). To identify the signals responsible for HSC formation, here we use single cell RNA-sequencing to simultaneously analyze the transcriptional profiles of AGM-derived cells transitioning from hemogenic endothelium to HSCs, and AGM-derived endothelial cells which provide signals sufficient to support HSC maturation and self-renewal. Pseudotemporal ordering reveals dynamics of gene expression during the hemogenic endothelium to HSC transition, identifying surface receptors specifically expressed on developing HSCs. Transcriptional profiling of niche endothelial cells identifies corresponding ligands, including those signaling to Notch receptors, VLA-4 integrin, and CXCR4, which, when integrated in an engineered platform, are sufficient to support the generation of engrafting HSCs. These studies provide a transcriptional map of the signaling interactions necessary for the development of HSCs and advance the goal of engineering HSCs for therapeutic applications.2022-01-01T00:00:00Z2022 Mar2026-05-09T23:43:39.802Z2025-04-04T22:14:03.093ZS-EPMC89482493533212510.1038/s41467-022-28781-z